The role of CXCR7, a seven-transmembrane G-protein coupled chemokine receptor, which binds with high affinity to chemokine CXCL11 and CXCL12 in oral cancer cells and the effect of transient CXCR7-downregulation on proliferation and migration of oral squamous cell carcinoma (OSCC) cells have not been reported. The aim of the present study was to evaluate the effects of CXCR7 on an OSCC cell line. In this study, we down-regulated CXCR7 in the KOSCC25B OSCC cell line by siRNA. In vitro cell proliferation and migration assays were used to investigate the effect of CXCR7- downregulation on cell proliferation and migration in si.KOSCC25B cells. The CXCR7 down-regulated OSCC cells grew significantly slower than the negative control siRNA transfected KOSCC25B cells (p<0.05). Additionally, migration of si.KOSCC25B cells decreased significantly compared with non-transfected KOSCC25B cells (p<0.007). These results suggest that down-regulation of CXCR7 induces anti-proliferative and anti-migratory effects in OSCC, and that CXCR7 may be a useful target molecule for the treatment of OSCC.